Cyclophosphamide-Potentiated West Nile Viral Encephalitis: Relative Influence of Cellular and Humoral Factors

Abstract

Intraperitoneal inoculation of 10⁶ LD₅₀ of West Nile virus produces an inapparent infection in the central nervous system of the mouse; the infection is converted into lethal encephalitis by a single dose of cyclophosphamide (150 mg/kg) given 24 hr after infection. Cyclophosphamide-potentiated infection is characterized by suppressed response of neutralizing antibody, prolonged viremia, enhanced titers of virus in the brain, and concomitant histologic encephalitis; death occurs eight to 16 days after infection. A single intraperitoneal injection of immune serum given as late as six days after infection reduces mortality to 15%. A comparable reduction in mortality follows the transfer of 10⁸ syngeneic splenocytes from mice immune to West Nile virus. However, these cells are effective only when given within two days after infection. In this model neutralizing antibody appears to play a critical role in recovery from potentially fatal encephalitis, and immune lymphoid cells may act primarily through production of antibody.